Electronic field effect detection of SARS-CoV-2 N-protein before the onset of symptoms.

As part of the efforts to contain the pandemic, researchers around the world have raced to develop testing platforms to detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the Coronavirus disease 2019 (COVID-19). Within the different detection platforms studied, the field effect transistor (FET) is a promising device due to its high sensitivity and fast detection capabilities. In this work, a graphene-based FET which uses a boron and nitrogen co-doped graphene oxide gel (BN-GO gel) transducer functionalized with nucleoprotein antibodies, has been investigated for the detection of SARS-CoV-2 nucleocapsid (N)-protein in buffer. This biosensor was able to detect the viral protein in less than 4 min, with a limit of detection (LOD) as low as 10 ag/mL and a wide linear detection range stretching over 11 orders of magnitude from 10 ag/mL-1 µg/mL. This represents the lowest LOD and widest detection range of any COVID-19 sensor and thus can potentially enable the detection of infected individuals before they become contagious. In addition to its potential use in the COVID-19 pandemic, our device serves as a proof-of-concept of the ability of functionalized BN-GO gel FETs to be used for ultrasensitive yet robust biosensors.

Evaluation of the therapeutic effect of propolis on Fasciola gigantica and Clostridium novyi type B infections in sheep.

The use of natural products for disease control is a promising approach to solving the problem of drug resistance. The aim of the research reported here was to evaluate the fasciolicidal and anti-Clostridium novyi type B activities of propolis administered orally to sheep infected with Fasciola gigantica and C. novyi type B. Sheep infected with both pathogens were divided into two groups: an infected treated group and an infected non-treated group. The treatment was oral administration of 50 mg propolis extract/kg daily for 15 days. The body weight of the sheep, fecal egg counts of F. gigantica, serum levels of F. gigantica IgG, concentrations of cytokines (IL-2, IL-10, and IL-17), and bacterial counts of C. novyi were evaluated. Following treatment, the sheep had increased body weight and a significant decrease in the egg count, which was reduced by 54.54% at 15 days post treatment. The level of anti- Fasciola IgG increased, whereas levels of IL-2, IL-10, and IL-17 decreased in propolistreated sheep. Treatment of sheep with propolis produced a significant reduction in fecal count of C. novyi, from 8 × 109 to 3 × 103 colony units per gram at 15 days post treatment. This research highlights the therapeutic potential of Egyptian propolis extract as a treatment against F. gigantica and C. novyi type B infections, and investigated its mode of action through its effect on some cellular and humoral responses in sheep with both infections.

An ultrasensitive heart-failure BNP biosensor using B/N co-doped graphene oxide gel FET.

Heart failure (HF) is the number one cause of death in the world. B-type natriuretic peptide (BNP) is a recognized biomarker for HF and can be used for early detection. Field effect transistor (FET) biosensors have the ability to sense BNP in much shorter times than conventional clinical studies. The lowest limit of detection (LOD) of state-of-the-art HF FET biosensors is 100 fM and detection ranges are short, being less than 4 orders of magnitude. In this work, a B/N co-doped graphene oxide (GO) gel (BN-GO) was used as the channel material in an FET biosensor targeting BNP. The sensor was able to sense BNP in as little as 2 min, with an LOD as low as 10 aM and a wide linear detection range of 10 aM-1 µM, stretching over 11 orders of magnitude. The biosensor showed great selectivity and minimal response towards K+ and OH- ions and the human epidermal growth factor receptor (HER2) protein. This biosensor serves as a proof-of-concept of the ability of BN-GO gel FETs to be used for ultrasensitive biosensors.

Evaluation of the therapeutic effect of propolis on Fasciola gigantica and Clostridium novyi type B infections in sheep

@#The use of natural products for disease control is a promising approach to solving the problem of drug resistance. The aim of the research reported here was to evaluate the fasciolicidal and anti-Clostridium novyi type B activities of propolis administered orally to sheep infected with Fasciola gigantica and C. novyi type B. Sheep infected with both pathogens were divided into two groups: an infected treated group and an infected non-treated group. The treatment was oral administration of 50 mg propolis extract/kg daily for 15 days. The body weight of the sheep, fecal egg counts of F. gigantica, serum levels of F. gigantica IgG, concentrations of cytokines (IL-2, IL-10, and IL-17), and bacterial counts of C. novyi were evaluated. Following treatment, the sheep had increased body weight and a significant decrease in the egg count, which was reduced by 54.54% at 15 days post treatment. The level of anti- Fasciola IgG increased, whereas levels of IL-2, IL-10, and IL-17 decreased in propolistreated sheep. Treatment of sheep with propolis produced a significant reduction in fecal count of C. novyi, from 8 × 109 to 3 × 103 colony units per gram at 15 days post treatment. This research highlights the therapeutic potential of Egyptian propolis extract as a treatment against F. gigantica and C. novyi type B infections, and investigated its mode of action through its effect on some cellular and humoral responses in sheep with both infections.

Quasi-Static Pull-in: an Instability in Electrostatic Actuators.

We identify a new instability in electrostatic actuators dubbed quasi-static pull-in. We report experimental evidence of the instability and study its characteristics in two types of micro actuators operating in ambient air. We found that the underlying mechanism is a fast-slow dynamic interaction between slowly-varying electrostatic excitation and fast resonator response that instigate large non-resonant oscillatory orbits and eventually disappears in a global Shilnikov bifurcation. Based on these findings, we formulate and present a new taxonomy of pull-in instabilities in electrostatic actuators.

Out-of-Plane Continuous Electrostatic Micro-Power Generators.

This paper presents an out-of-plane electrostatic micro-power generator (MPG). Electret-based continuous MPGs with different gaps and masses are fabricated to demonstrate the merits of this topology. Experimental results of the MPG demonstrate output power of 1 mW for a base acceleration amplitude and frequency of 0.08 g and 86 Hz. The MPGs also demonstrate a wideband harvesting bandwidth reaching up to 9 Hz. A free-flight and an impact mode model of electrostatic MPGs are also derived and validated by comparison to experimental results.

Falls in elderly hemodialysis patients.

The elderly, (age ≥ 65 years) hemodialysis (HD) patient population is growing rapidly across the world. The risk of accidental falls is very high in this patient population due to multiple factors which include aging, underlying renal disease and adverse events associated with HD treatments. Falls, the most common cause of fatal injury among elderly, not only increase morbidity and mortality, but also increase costs to the health system. Prediction of falls and interventions to prevent or minimize fall risk and associated complications will be a major step in helping these patients as well as decreasing financial and social burdens. Thus, it is vital to learn how to approach this important problem. In this review, we will summarize the epidemiology, risk factors, pathophysiology and complications of falls in elderly HD patients. We will also focus on available methods to assess and predict the patients at higher risk of falling and will provide recommendations for interventions to reduce the occurrence of falls in this population.

An unusual case of anti-glomerular basement membrane disease presenting with nephrotic syndrome.

Anti-glomerular basement membrane (anti-GBM) disease is a vasculitic disease characterized by acute kidney injury, oliguria, hematuria and proteinuria. Proteinuria is rarely in the nephrotic range. A case of anti-GBM disease with proteinuria of 22.5 g/day is discussed. Immunofluorescence showed strong linear IgG deposits while electron microscopy showed widespread visceral epithelial cell foot cell process effacement. No electron dense immune complex-type deposits were identified. Pathology findings were not suggestive of simultaneous presentation of anti-GBM disease and other diseases associated with nephrotic range proteinuria. Anti-GBM disease should be considered in a comprehensive differential diagnosis of severe proteinuria.

Management of TB in the Private Sector in Khartoum; Sudan: Quality and Impact on TB Control

Introduction: Sudan has a large and growing private health sector. No survey was done in Sudan to show the extent of the use of private health care services by the population. Also precise data on tuberculosis (TB) diagnosis and treatment in the private sector are not available. Material and methods A facility-based cross-sectional survey was carried out during February2007-June 2007 in Khartoum state; whereby consented private physicians working in the all private clinics (n=110) were interviewed. Results This study showed that a large private sector exist in the country and deliver care to TB patients and reported the non-adherence of this sector to National Tuberculosis Program (NTP) guidelines. 59.1of the interviewed physicians correctly mentioned the TB treatment regimens; only 8(12.3) physicians that reported management of TB patients actually prescribed these regimens to their patients. Similarly; only 10(15.4) physicians requested sputum smear examination for TB diagnosis. Conclusion A considerable proportion of cases is inadequately managed by the private sector and is not notified to NTP. The information delivered by this study can be used to develop a workable Public-private mix (PPM) model with the private sector

Molluscicidal saponins from leaves of Hedera canariensis.

Activity-guided fractionation of the methanol extract of Hedera canariensis (var. Gloire de Maringo) Wild leaves afforded five saponins 1-5. Chemical and spectral methods (MS, 1HNMR, 13CNMR) showed that they are glycosides of hederagenin and oleanolic acid. The results showed that 4,5 exhibited molluscicidal properties, compound 1 was inactive. Mortality rate of exposed snails increased by increasing plant extract concentration. Lymnaea cailliaudi was more sensitive to plant extract than Biomphalaria alexandrina. The histopathological study revealed distinct damage in the structure of the stomach and ovotestis of treated L. cailliaudi snails. Saponin content was determined in term of haemolytic index.

Pathogenesis of focal glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is the histologic expression of diverse processes affecting the renal glomeruli and occurring in primary and secondary forms. A number of pathogenic factors have been identified in primary FSGS, and multiple etiologies have been defined as contributing factors for the development of secondary FSGS. There is a complex interplay between etiologic and pathogenic factors, progression factors and intervention in the phenotypic expression of FSGS. Key components include genetic predisposition, environmental influences and the impact on phenotype of pharmacologic intervention. The phenotypic spectrum for FSGS ranges from mild proteinuria and slow progression to a devastating clinical syndrome characterized by heavy proteinuria and rapid loss of renal function over a period of months. While the pathogenesis is unknown, much is known about factors which are involved in the development and progression of both primary and secondary FSGS. The ultimate goal of understanding pathogenesis is to provide specific nontoxic therapy for those patients who have a definable form of FSGS. While this goal is not yet in sight, many types of intervention, not addressed in the current chapter, can influence the course of various diseases presenting as FSGS. Until specific therapy can be fashioned, it is necessary for the clinician caring for these patients to appreciate the complex interaction of pathogenetic factors involved in the development and pregression of FSGS, as a rationale for providing intervention to prevent development of the disease and to slow its course.

Isolation and structural characterization of Toxocara vitulorum specific antigen and its potency in diagnosis of toxocariasis among buffalo calves.

A method of affinity chromatography purification of species-specific antigen from Toxocara vitulorum adult worm is described. The purification process resulted in a fraction with 9315 fold increase in specific activity compared to crude extract. Structural characterization of the isolated fraction by SDS polyacrylamide gel electrophoresis, isoelectric focusing and amino acid analysis showed that the fraction consists of only two polypeptides of 92 kD and 87 kD with isoelectric points of 8.8 and 8.9. Moreover, 17 amino acids were identified in the fraction with high proportions of only three of them (tyrosine, glycine and glutamic). The isolated antigen proved potency in the diagnosis of toxocariasis among buffalo claves using ELISA which recorded 100% sensitivity.

Molecular identity of major cross-reactive adult antigens in Fasciola gigantica, Toxocara vitulorum and Moniezia expansa.

Cross reactivity between Fasciola gigantica, Toxocara vitulorum and Moniezia expansa whole worm extracts was proved by ELISA. Intense cross-reaction was observed between F. gigantica and M. expansa rather than between each of them and T. vitulorum. As judged by immunoblot, the cross-reactive antigens in F. gigantica which recognized by T. vitulorum antisera was 109 kD while this component in addition to another one of 52 kD were detected by M. expansa sera in the same extract. Furthermore, T. vitulorum antigen which cross-reacted with F. gigantica was 133 kD and with M. expansa was 143 kD. Antigens responsible for cross-reactivity in M. expansa were 130 kD and 210 kD to T. vitulorum and F. gigantica respectively.

Structural characterization and immunolocalization of egg antigens cross-react with Toxocara vitulorum, Fasciola gigantica and Moniezia expansa mature flukes.

A structural homology between eggs of Toxocara vitulorum, Fasciola gigantica and Moniezia expansa was proved by the use of SDS-PAGE. In immunoblot, 9, 11 and 7 polypeptides were recognized in F. gigantica, M. expansa and T. vitulorum eggs respectively by their respective rabbit anti-adult antisera. Moreover, components of 240 KD and 206 KD were recognized in the three eggs by different anti-adult antisera. The anatomic localization of the crossreactive epitopes in eggs was determined by indirect immunofluorescence microscopy. The cross-reactive epitopes were mainly associated with embryonted cells of F. gigantica, egg shell, larvae and vitelline membranes of T. vitulorum and egg shall and granular layer of M. expansa.

Antibiotic resistance and prevalence of beta-lactamase in Haemophilus influenzae isolates-a surveillance study of patients with respiratory infection in Saudi Arabia.

Haemophilus influenzae was isolated from patients with respiratory tract infections in five centers in Saudi Arabia. All of the 129 isolates tested by MIC agar dilution were fully susceptible to ceftazidime and ciprofloxacin but 13.2% were resistant to ampicillin, 7% to tetracycline, 5.4% to chloramphenicol, 3.9% to roxithromycin, and 1.6% to amoxicillin/clavulanic acid. Seventeen (13.2%) of all isolates produced TEM-1 type beta-lactamase, the majority (82%) characterized as biotype I or II with 4 (23.5%) encapsulated and belonging to serotype b. There was a clear distinction between the prevalence of beta-lactamase production in hospital patients (26.3% of 19 isolates) compared with community based patients (10.9% of 110 isolates). In addition, we report an increase in the prevalence of beta-lactamase negative, ampicillin intermediate strains (BLNAI) compared to previous studies in this defined geographical region. Changes in the frequency and nature of antimicrobial resistance in common respiratory pathogens confirms the need to maintain surveillance.

Depletion of total antioxidant capacity in type 2 diabetes.

The purpose of the study was to examine the relationship between antioxidant depletion, glycemic control, and development of chronic complications in a controlled population of type 2 diabetic patients. Fifty age-matched type 2 diabetic patients receiving sulfonylureas but not insulin treatment were screened and assigned to two groups based on the presence or absence of proteinuria. A third group of normal subjects without diabetes were also enrolled in the study. All subjects in the three groups were Egyptians who were matched for body weight, and the two diabetic groups were also age-matched. Plasma glucose and fructosamine levels were higher in the two groups of diabetic patients versus the control group, but lipid peroxide levels were higher only in the patients with proteinuria. Compared with the control group, the total antioxidant capacity was depleted in the two diabetic groups, but the depletion was more severe in patients with proteinuria. Thus, the mean Trolox equivalent antioxidant capacity (TEAC) of the control group was 2.7+/-0.45, versus 1.7+/-0.5 (P < .001) in the patients without proteinuria. Furthermore, the TEAC measured in patients with proteinuria, who also had more diabetic complications, was lower (1.4+/-0.5, P < .001) than the TEAC in patients without urinary protein. In conclusion, a depletion of the total antioxidant capacity is associated with a higher incidence of diabetic complications.

Angiotensin II and nitric oxide: a question of balance.

The vasoconstrictor peptide angiotensin II (Ang II) and the endogenous vasodilator nitric oxide (NO) have many antagonistic effects, as well as influencing each other's production and functioning. In the short-term, Ang II stimulates NO release, thus modulating the vasoconstrictor actions of the peptide. In the long-term, Ang II influences the expression of all three NO synthase (NOS) isoforms, while NO downregulates the Ang II Type I (AT1) receptor, contributing to the protective role of NO in the vasculature. Within the cardiovascular system, Ang II and NO also have antagonistic effects on vascular remodeling and apoptosis. In the kidney, the distribution of the NOS isoforms coincides with the sites of the components of the renin-angiotensin system. NO influences renin secretion from the kidney, and NO-Ang II interactions are important in the control of glomerular and tubular function. In the adrenal gland, NO has been shown to affect Ang II-induced aldosterone synthesis, while in the brain NO appears to influence Ang II-induced drinking behavior, although conflicting data have been reported. In this review, we focus on the diverse ways in which Ang II and NO interact, and on the importance of maintaining a balance between these two important mediators.

Elevated serum levels of tumor necrosis factor alpha in normal-weight women with polycystic ovary syndrome.

Since an increase in tumor necrosis factor alpha (TNFalpha) expression has been associated with insulin resistance, this study was undertaken to determine the status of circulating TNFalpha and the relationship of TNFalpha with insulin levels, body weight, or both in women with polycystic ovary syndrome (PCOS). Fasting serum samples were analyzed in 34 subjects with PCOS, of whom 22 were obese (body mass index [BMI]>27 kg/m2), and in 40 normal control women, of whom 20 were obese. Women with PCOS exhibited a significantly (P<.02) higher mean serum TNFalpha concentration compared with the controls. The serum TNFalpha level and BMI were directly correlated in women with PCOS (r=.48, P<.005) and highly correlated in controls (r=.78, P<.001). When subjects were classified by body weight, the mean serum TNFalpha concentration was significantly (P<.001) elevated in normal-weight women with PCOS compared with normal-weight controls. On the other hand, mean serum TNFalpha concentrations in obese women with PCOS and obese controls were similar and significantly (P<.02) higher than in normal-weight women with PCOS. A direct correlation between serum fasting insulin and TNFalpha was evident in controls (r=.35, P<.03), but not in women with PCOS. However, in the subgroup of obese women with PCOS, fasting insulin directly correlated (r=.49, P<.03) with TNFalpha and the median fasting serum insulin concentration was significantly (P<.05) higher compared with the level in normal-weight women with PCOS and all controls. Fasting insulin and TNFalpha were no longer correlated in controls as a group and in obese women with PCOS when controlling for body weight. Serum TNFalpha did not correlate with luteinizing hormone (LH), testosterone (T), or dehydroepiandrosterone sulfate (DHEAS) in women with PCOS. However, serum insulin was significantly correlated (r=.49, P<.0004) with T and the BMI exhibited a trend for correlation with serum T (r=.33, P=.05) in women with PCOS. Finally, the mean serum LH concentration was significantly (P<.02) higher in normal-weight women with PCOS versus obese women with PCOS, and serum LH levels exhibited a trend for an inverse correlation with the BMI (r=.31, P=.09) in women with PCOS. We conclude that (1) serum TNFalpha is increased in normal-weight women with PCOS and is even higher in obese individuals regardless of whether they have PCOS; (2) factors other than obesity are the cause of elevated serum TNFalpha in normal-weight women with PCOS; and (3) whereas increased circulating TNFalpha may mediate insulin resistance in obesity, which may in turn promote hyperandrogenism in obese women with PCOS, it remains to be demonstrated whether this is also the case in normal-weight women with PCOS.

Three-dimensional dynamic behaviour of the human knee joint under impact loading.

The objective of this study is to determine the three-dimensional dynamic response of the human knee joint. A three-dimensional anatomical dynamic model was thus developed and consists of two body segments in contact (the femur and tibia) executing a general three-dimensional dynamic motion within the constraints of the different ligamentous structures. Each of the articular surfaces at the tibio-femoral joint was represented mathematically by a separate mathematical function. The joint ligaments were modelled as nonlinear elastic springs. The six-degrees-of-freedom joint motions were characterized by using six kinematic parameters, and ligamentous forces were expressed in terms of these six parameters. Knee response was studied by considering sudden external forcing pulse loads applied to the tibia. Model equations consist of nonlinear second-order ordinary differential equations coupled with nonlinear algebraic constraint conditions. Constraint equations were written to maintain at least one-point contact throughout motion; one- and two-point contact versions of the model were developed. This Differential-Algebraic Equations (DAE) system was solved by employing a DAE solver: the Differential/Algebraic System Solver (DASSL) developed at Lawrence Livermore National Laboratory. A solution representing the response of this three-dimensional dynamic system was thus obtained for the first time. Earlier attempts to determine the system's response were unsuccessful owing to the inherent numerical instabilities in the system and the limitations of the solution techniques. Under the conditions tested, evidence of "femoral roll back" on both medial and lateral tibial plateaus was not observed from the model predictions. In the range of 20 degrees to 66 degrees of knee flexion, the lateral tibial contact point moved posteriorly while the medial tibial contact point moved anteriorly. In the range of 66 degrees to 90 degrees of knee flexion, contact was maintained only on the medial side and the tibial contact point (on the medial side) continued to move anteriorly. It was further found that increasing pulse amplitude and/or duration caused a decrease in the magnitude of the tibio-femoral contact force at a given flexion angle. These results suggest that increasing load level caused a decrease in joint stiffness. The results of this study also show that the anterior fibres of the posterior cruciate and the medial collateral ligaments are the primary restraints for a posterior forcing pulse in the range of 20 degrees to 90 degrees of knee flexion; this explains why most isolated posterior cruciate ligament injuries and combined injuries to the posterior cruciate and the medial collateral result from a posterior impact on a flexed knee.